Comment: A chink in the armour of HIV

The announcement made last week that two HIV-infected men in Boston were able to stop their anti-HIV drugs without evidence of the virus returning has not surprisingly made headlines across the world. Coming so soon after the equally heavily publicised cases this year of the "functionally" cured the Mississippi Baby and the 14 adults living with HIV in France who are all doing well some nine years after being taken off antiretrovirals, it is understandably generating a public perception that perhaps we are in fact inching closer to a cure for HIV. But for those of us working in the field, all these cases raise as many questions as they answer.

So where does that leave us? Where exactly are we in terms of finding a cure for HIV? And why is the search for a cure back on the agenda at a time when current treatments for HIV, called antiretrovirals, taken at the right time are able to provide people living with HIV with a normal life expectancy?

Antiretrovirals have delivered one of the most spectacular scientific advances in recent decades. They can block the virus from infecting new cells and very effectively keep the virus under control for many years. These highly effective drugs significantly prolong life and at the same time dramatically reduce a person's infectiousness. They have literally saved millions of lives, families and communities.

But the drugs have their limits; if the antiretrovirals are stopped, the virus resurfaces in the blood – on average within three to four weeks. This happens because the virus can hide in certain blood cells and can essentially go to sleep and become invisible to the drugs and the patient's immune system. These long lived "reservoirs" of virus persist indefinitely. Therefore, patients require life long treatment – which comes with substantial costs and some long term side effects.

There are currently 33-million people living with HIV – all of whom at some stage will require antiretrovirals. In 2012, close to 10-million people in low and middle income countries were receiving antiretrovirals – another great success story. But the costs of maintaining this and increasing access to the many more that need treatment are now substantial. Health systems and funding bodies are already struggling to foot the bill.

Finding a cure for HIV – or a way for patients to safely stop antiretrovirals and keep the virus under control – will therefore have a very significant economic and personal impact.

The big challenge is this: how to find a way to permanently knock out these last reservoirs of the virus.

Lessons from Boston patients
So what do the Boston patients bring to the table in the jigsaw of HIV cure research?

For one, we know that after a stem cell transplant, the foreign blood cells slowly eliminate the patient's own blood cells. This is how the stem cell transplant controlled the lymphoma in the Boston patients. These new foreign blood cells were protected from infection because the patients were taking antiretrovirals. The patients' doctors then asked an important question – did the foreign blood cells also eliminate the HIV reservoir? The answer appeared to be a resounding yes: as early as six months post-transplant.

But because the virus can hide only to re-emerge once antiretrovirals are ceased, the critical question was what would happen if and when those drugs were in fact ceased. What we know so far is that when patients were tested at eight weeks and then again at 15 weeks after stopping the antiretrovirals, neither patient had evidence of virus detected in their blood.

Does this mean they are truly cured? This is harder to answer and as the researchers acknowledged in Kuala Lumpur, we'll be able to draw much more solid conclusions after 12 months, perhaps even two years. It is probably more accurate to say that the two patients are in remission, a cautious word but a more realistic one because we just don't know at this stage of the game if and when the virus will return.

One lesson the Boston patients definitely do not teach is that anyone with HIV infection should now be lining up for a stem cell transplant. Transplantation is a high risk procedure with over 20% mortality. The Boston patients had the transplants because they had lymphoma – not because they had HIV.

New research
But these cases will open up new avenues of research. Can we modify the transplant procedure to eliminate the HIV reservoir but not totally wipe out the patient's own cells? Could the same result be achieved with some but not all of the complex treatment? Can this outcome be mimicked with a vaccine that activates the patient's own immune response against the reservoir?

Globally, multiple ideas are already being tested to tackle the formidable HIV reservoir – waking the virus up or ensuring the virus sleeps forever, and even using gene therapy to effectively make a patient's cells permanently resistant to HIV. It's early days, but the scientific advances since the International Aids Society launched the Towards an HIV Cure initiative three years ago have been impressive.

The Boston patients have taught us that HIV can indeed go into remission – and might even one day be cured. The challenge now will be the why and how, and ultimately the use of this knowledge to find new drugs to develop a cure for all people living with HIV – rich or poor. These are just the first steps down a long road ahead but they are vital ones.

Sharon Lewin is professor and head of the department of infectious diseases at the Alfred Hospital and Monash University. She is also co-head of the Centre for Biomedical Research at the Burnet Institute, in Melbourne, Australia. She is the local co-chair of the 20th International Aids Conference (Aids 2014) taking place in Melbourne from July 20 to 25 in 2014.

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